Spectral heart rate variability and selected biochemical markers for autonomic activity in rats under pentobarbital anesthesia
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Chair and Department of Pathophysiology, Jagiellonian University Medical College, Krakow, Poland
Department of Virology, Chair of Microbiology, Jagiellonian University Medical College, Krakow, Poland
Chair and Department of Human Physiology and Pathophysiology, Faculty of Medicine, University of Rzeszow, Poland
Submission date: 2016-07-22
Acceptance date: 2017-01-31
Online publication date: 2017-07-05
Publication date: 2019-12-20
Corresponding author
Łukasz Dobrek   

Chair and Department of Pathophysiology, Jagiellonian University Medical College, Czysta 18, 31-121 Krakow, Poland. Tel.: +48 12 632 90 56; fax: +48 12 632 90 56.
Pol. Ann. Med. 2017;24(2):180-187
Autonomic nervous system (ANS) function can be evaluated by analysis of heart rate variability (HRV) and plasma concentration of noradrenaline (NA). Recent studies identified potential, biochemical markers of the ANS activity, including selected co-transmitters, released from either sympathetic (e.g. neuropeptide Y – NPY) or parasympathetic (e.g. vasoactive intestinal peptide – VIP) fibers.

The aim of the study was to analyze HRV recordings and to determine plasma level of NA, NPY and VIP in 3–12 months males and females rats under pentobarbital anesthesia. Moreover, our goal was to determine overall and gender-dependent correlation between the HRV indices and abovementioned compounds.

Material and methods:
The experiment included 36 rats with different autonomic tone related to age and gender. Spectral HRV analysis was applied and NA, NPY and VIP were measured by ELISA.

Results and discussion:
Male rats were characterized by significantly higher values of selected HRV indices: total power (TP), very low frequency (VLF) and high frequency (HF) and plasma concentrations of both analyzed neuropeptides comparing to female ones. Similar to the overall assessment, both males and females showed significant correlations between NA and TP, VLF and LF. Moreover, male rats (but not female ones) presented with significant moderate correlations between NPY and LF, VIP and TP, HF and normalized HF (nHF).

Our preliminary findings imply that NA correlates with global autonomic activity (TP) and with the values of sympathetically-driven components (VLF and LF). Furthermore, VIP seems to correlate with specific measures of parasympathetic drive (HF and nHF), but only in male rats.

None declared.
Chowdhury D, Patel N. Approach to a case of autonomic peripheral neuropathy. JAPI. 2006;54:727–732.
Vinik AI, Maser RE, Mitchell BD, Freeman R. Diabetic autonomic neuropathy. Diabetes Care. 2003;26:1553–1579.
Freeman R. Assessment of cardiovascular autonomic function. Clin Neurophysiol. 2006;117(4):716–730.
Mathias CJ. Autonomic diseases: clinical features and laboratory evaluation. J Neurol Neurosurg Psychiatry. 2003;74(suppl III):31–41.
Dobrek Ł, Thor P. Current concepts in clinical and laboratory assessments of autonomic nervous systemactivity. J Pre-Clin Clin Res. 2015;9(1):63–68.
Malik M (ed.) Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of The European Society of Cardiology and The North American Society of Pacing and Electrophysiology. Eur Heart J. 1996; 17 (3), 354–381.
Berntson GG, Bigger Jr JT, Eckberg DL, et al. Heart rate variability: origins, methods, and interpretive caveats. Psychophysiology. 1997;34(6):623–648.
Goldstein DS. Catecholamines. Clin Auton Res. 2010;20(6):331–352.
Goldstein DS, Eisenhofer G, Kopin IJ. Sources and significance of plasma levels of catechols and their metabolites in humans. J Pharmacol Exp Ther. 2003;305:800–811.
Burnstock G. Cotransmission. Curr Opin Pharmacol. 2004;4(1):47–52.
Cheng Y, Cohen B, Oréa V, Barres C, Julien C. Baroreflex control of renal sympathetic nerve activity and spontaneous rhythms at Mayer wave's frequency in rats. Auton Neurosci. 2004;111(2):80–88.
Matsukawa K, Ninomiya I. Anesthetic effects on tonic and reflex renal sympathetic nerve activity in awake cats. Am J Physiol. 1989;256(Pt 2):R371–R378.
Matsukawa K, Ninomiya I, Nishiura N. Effects of anesthesia on cardiac and renal sympathetic nerve activities and plasma catecholamines. Am J Physiol. 1993;265(Pt 2):R792–R797.
Shimokawa A, Kunitake T, Takasaki M, Kannan H. Differential effects of anesthetics on sympathetic nerve activity and arterial baroreceptor reflex in chronically instrumented rats. J Auton Nerv Syst. 1998;72(1):46–54.
Recommended Methods of Anesthesia, Analgesia, and Euthanasia for Laboratory Animal Species. Albert Einstein College of Medicine, Institute for Animal Studies. Van Etten. 2016;460(718):839–7100 (accessed 28.12.2016).
Aubert AE, Ramaekers D, Beckers F, et al. The analysis of heart rate variability in unrestrained rats. Validation of method and results. Comput Methods Progr Biomed. 1999;60:197–213.
Goncalves H, Henriques-Coelho T, Bernardes J, Rocha AP, Brandao-Nogueira A, Leite-Moreira A. Analysis of heart rate variability in a rat model of induced pulmonary hypertension. Med Eng Phys. 2010;32:746–752.
Dobrek Ł, Kaszuba-Zwoińska J, Baranowska A, Skowron B, Thor P. Resting heart rate variability and plasma noradrenaline level as a measurement of autonomic nervous system activity in mature, aging rats. J Pre-Clin Clin Res. 2016;10(1):50–56.
Bernardi L, Valle F, Coco M, Calciati A, Sleight P. Physical activity influences heart rate variability and very-lowfrequency component in Holter electrocardiograms. Cardiovasc Res. 1996;32(2):234–237.
Taylor JA, Carr DL, Myers CW, Eckberg DL. Mechanisms underlying very low frequency RR-interval oscillations in humans. Circulation. 1998;98:547–555.
Silva Soares P, da Nobrega ACL, Ushizima MR, Irigoyen MCC. Cholinergic stimulation with piridostigmine increases heart rate variability and baroreflex sensitivity in rats. Auton Neurosci. 2004;113:24–31.
Goldstein DS, McCarty R, Polinsky RJ, Kopin IJ. Relationship between plasma norepinephrine and sympathetic neural activity. Hypertension. 1983;5(4):552–559.
Hubbard JW, Buchholz RA, Keeton TK, Nathan MA. Plasma norepinephrine concentration reflects pharmacological alternation of sympathetic activity in the conscious cat. J Auton Nerv Syst. 1986;15(1):93–100.
Pedrazzini T, Pralong F, Grouzmann E, Neuropeptide Y. The universal soldier. Cell Mol Life Sci. 2003;60:350–377.
Igarashi H, Fujimori N, Ito T, et al. Vasoactive intenstinal peptide (VIP) and VIP receptors – elucidation of structure and function for therapeutic applications. Int J Clin Med. 2011;2:500–508.
Culp DJ, Richardson LA. Regulation of mucous acinar exocrine secretion with age. J Dent Res. 1996;75(1):575–580.
Lundberg JM, Franco-Cereceda A, Hemsen A, Lacroix JS, Pernow J. Pharmacology of noradrenaline and neuropeptide tyrosine (NPY)-mediated sympathetic cotransmission. Fundam Clin Pharmacol. 1990;4(4):373–391.
Strata P, Harvey R. Dale's principle. Brain Res Bull. 1999;50:349–350.
Cernuda-Morollon E, Martinez-Camblor P, Alvarez R, Larosa D, Ramon C, Pascual J. Increased VIP levels in peripheral blood outside migraine attacks as a potential biomarker or cranial parasympathetic activation in chronic migraine. Cephalalgia. 2015;35(4):310–316.
Drummond PD, Finch PM, Edvinsson L, Goadsby J. Plasma neuropeptide Y in the symptomatic limb of patients with causalgic pain. Clin Auton Res. 1994;4:113–116.
Magnussen C, Hung SP, Ribeiro-da-Silva A. Novel expression pattern of neuropeptide Y immunoreactivity in the peripheral nervous system in a rat model of neuropathic pain. Mol Pain. 2015;11:31.
Poncet MF, Damase Michel C, Tavernier G, et al. Changes in plasma catecholamine and neuropeptide Y levels after sympathetic activation in dogs. Br J Pharmacol. 1992;105:181–183.
Dawidson I, Blom M, Lundeberg T, Theodorsson E, Angmar- Mansson B. Neuropeptides in the saliva of healthy subjects. Life Sci. 1997;60(4–5):269–278.
Naito T, Itoh H, Takeyama M. Effects of Hange-koboku-to on neuropeptide levels in human plasma and saliva. Biol Pharm Bull. 2003;26(11):1609–1613.
Satoh Y, Itoh H, Takeyama M. Effects of bakumondoto on neuropeptide levels in human saliva and plasma. J Trad Med. 2009;26(3):122–130.
El-Sayed ZA, Mostafa GA, Aly GS, El-Shahed GS, Abd El-Aziz MM, El-Emam SM. Cardiovascular autonomic function assessed by autonomic function tests and serum autonomic neuropeptides in Egyptian children and adolescents with rheumatic diseases. Rheumatology. 2009;48(7):843–848.
Baum D, Halter JB, Taborsky Jr GJ, Porte Jr D. Pentobarbital effects on plasma catecholamines: temperature, heart rate, and blood pressure. Am J Physiol Endocrinol Metab. 1985;248(1):E95–E100.
Hanamoto H, Niwa H, Sugimura M, Morimoto Y. Autonomic and cardiovascular effects of pentobarbital anesthesia during trigeminal stimulation in cats. Int J Oral Sci. 2012;4:24–29.
Strzyżewska E, Szweda M. Podstawowe parametry fizjologiczne wybranych zwierząt laboratoryjnych oraz przegląd leków stosowanych u tych zwierząt. In: Szarek J, Szweda M, Strzyżewska E, eds. Zwierzęta laboratoryjne patologia i użytkowanie. Olsztyn: UWM; 2013 [in Polish].
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